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Plasma and Leukemic Cell Pharmacokinetics of High‐Dose N 4 ‐Behenoyl‐1‐β‐D‐arabinofuranosylcytosine in Acute Leukemia Patients
Author(s) -
Yoshida Takashi,
Kobayashi Kazumi,
Okabe Yoko,
Okumura Hirokazu,
Matano Sadaya,
Kanno Masatoshi,
Takeda Yasushi,
Ohtake Shigeki,
Nakamura Shinobu,
Matuda Tamotu
Publication year - 1994
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1994.tb03966.x
Subject(s) - pharmacokinetics , radioimmunoassay , cytarabine , high performance liquid chromatography , chemistry , leukemia , acute leukemia , antimetabolite , pharmacology , medicine , chromatography , chemotherapy
The pharmacokinetics of N 4 ‐behenoyl‐1‐β‐D‐arabinofuranosylcytosine (BHAC), a lipophilic antitumor analog of 1‐β‐D‐arabinofuranosylcytosine (ara‐C), was investigated, by assay of plasma and leukemic cells of ten acute leukemic patients receiving 60‐minute intravenous (IV) infusion of 700 mg/m 2 BHAC, for BHAC and 1‐β‐D‐arabinofuranosylcytosine 5′‐triphosphate (ara‐CTP) by high‐performance liquid chromatography, ara‐C by radioimmunoassay, and 1‐β‐D‐arabinofuranosyluracil (ara‐U) by gas chromatography‐mass fragmentography. The plasma concentration of BHAC reached a maximum (173.4 ± 75.3 μg/mL) at the end of the infusion and then declined in a biphasic pattern with an initial‐phase half‐life (t1/2α) of 1.00 ± .36 hours and a second‐phase half‐life (t1/2β) of 4.28 ± 2.35 hours. That of ara‐C similarly reached a maximum (102.2 ± 39.9 mg/mL) at the end of the infusion and then declined with t1/2α of 1.37 ± 1.11 hours and t1/2β of 11.2 ± 4.31 hours. Intracellular ara‐CTP concentration increased in a linear‐accumulation manner for the first 4 hours after the infusion, reached a maximum of .081 ± .112 μg/10 7 cells at approximately 7 hours, and then declined very slowly in accordance with a one‐compartment model with t1/2 of 13.56 ± 9.62 hours.